Expanded circulating peripheral helper T cells in systemic lupus erythematosus: association with disease activity and B cell differentiation

Rheumatology (Oxford). 2019 Oct 1;58(10):1861-1869. doi: 10.1093/rheumatology/kez077.

Abstract

Objective: Peripheral helper T (TPH) cells are a recently identified Th cell subset that promotes B cell differentiation and antibody production in inflamed tissues. This study investigated circulating TPH cells to determine their involvement in systemic lupus erythematosus (SLE).

Methods: Peripheral blood mononuclear cells collected from SLE patients and healthy individuals were analysed. TPH cells were identified as CD3+CD4+CD45RA-CXCR5- cells with a high expression of PD-1. The frequency, activation status and subsets of TPH cells were evaluated by flow cytometry. The production of IL-21 was assessed by intracellular staining and the association of TPH cells with disease activity and B cell populations was determined.

Results: Circulating TPH cells, identified as CD3+CD4+CD45RA-PD-1highCXCR5- cells were increased in the peripheral blood of SLE patients compared with controls. Circulating TPH cells produced similar amounts of IL-21 compared with follicular Th cells. The expansion and activation of TPH cells were correlated with SLE disease activity. Activated TPH cells, particularly Th1-type TPH cells, were associated with the promotion of B cell differentiation in SLE patients.

Conclusion: The association of TPH cells with disease activity suggests the involvement of extrafollicular T-B cell interactions in the pathogenesis of SLE. TPH cells promote autoantibody production in aberrant lymphoid organs and therefore might be a novel therapeutic target in autoantibody-producing disorders.

Keywords: B cell differentiation; disease activity; peripheral helper T cells; systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibody Formation / immunology
  • B-Lymphocytes / immunology*
  • Cell Differentiation / immunology*
  • Female
  • Humans
  • Interleukins / metabolism
  • Leukocytes, Mononuclear
  • Lupus Erythematosus, Systemic / immunology*
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Th1 Cells / immunology

Substances

  • Interleukins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • interleukin-21